ALIMTA Administration and Education Guide

Transcription

1 ALIMTA Administration and Education Guide A comprehensive guide that includes customizable dosing handouts for patients and caregivers ALIMTA is indicated for the initial treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NCLC) in combination with cisplatin. ALIMTA is indicated for the maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy, as a single agent. ALIMTA is indicated for the treatment of patients with recurrent metastatic nonsquamous non-small cell lung cancer (NCLC) after prior chemotherapy, as a single agent. Limitation of Use: ALIMTA is not indicated for the treatment of patients with squamous cell non-small cell lung cancer. ALIMTA is indicated, in combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma (MPM) whose disease is unresectable or who are otherwise not candidates for curative surgery. elect Important afety Information: Contraindication ALIMTA is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed. ee Important afety Information for ALIMTA for Consumers on page 7 and for Healthcare Providers on pages 8-9. For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information and Patient Prescribing Information.

2 Treatment with ALIMTA in combination with cisplatin 1st-line advanced nonsquamous* NCLC and MPM Dosing and administration for ALIMTA in combination with cisplatin: The recommended dose of ALIMTA is 500 mg/m 2 as an IV infusion over 10 minutes administered prior to cisplatin on day 1 of each 21-day cycle. II ALIMTA is indicated for the initial treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NCLC) in combination with cisplatin. Limitation of Use: ALIMTA is not indicated for the treatment of patients with squamous cell non-small cell lung cancer. ALIMTA is indicated, in combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma (MPM) whose disease is unresectable or who are otherwise not candidates for curative surgery. IV=intravenous; MPM=malignant pleural mesothelioma; NCLC=non-small cell lung cancer. * Includes adenocarcinoma, large cell carcinoma, and other histologies except those with squamous cell type. In patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 ml/min or greater. There is no recommended dose for patients whose creatinine clearance is less than 45 ml/min. For advanced NCLC, administer for up to six cycles in the absence of disease progression or unacceptable toxicity. II For MPM, administer until disease progression or unacceptable toxicity. 2 Vitamin Regimen One week prior to chemotherapy, then about every 9 weeks during treatment 21-Day Therapy Cycle A C Day 1 Day 12 Day 2 Day 13 Nurse Administered Day 3 Day 14 Day 4 Day 15 Day 5 Day 16 Day 6 Day 17 Day 7 Patient Administered Day 18 Day 8 Day 19 Day 9 Day 20 Day 10 Vitamin 1000 mcg injected intramuscularly (1 week prior to the first dose of ALIMTA, then once every third cycle thereafter). Do not substitute oral vitamin for intramuscular vitamin. A ALIMTA 500 mg/m 2 IV over 10 minutes (every 21 days) C Cisplatin Refer to the prescribing information for cisplatin Day 21 Folic Acid mcg PO daily (beginning 7 days preceding the first dose of ALIMTA, during full course of therapy, and for 21 days after the last dose of ALIMTA) Day 11 Dexamethasone 4 mg PO BID (the day before, the day (or equivalent) of, and the day after ALIMTA) Dosing modification notes In patients with creatinine clearances between 45 ml/min and 79 ml/min, avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of ALIMTA. Monitor patients more frequently for myelosuppression, renal, and gastrointestinal toxicity, if concomitant administration of ibuprofen cannot be avoided Obtain complete blood count on days 1, 8, and 15 of each cycle. Assess creatinine clearance prior to each cycle. Do not administer ALIMTA if the creatinine clearance is less than 45 ml/min Delay initiation of the next cycle of ALIMTA until recovery of nonhematologic toxicity to grade 0-2, absolute neutrophil count (ANC) is 1500 cells/mm 3 or higher, and platelet count is 100,000 cells/mm 3 or higher Upon recovery, modify the dosage of ALIMTA in the next cycle as specified in the full Prescribing Information For dosing modifications for cisplatin, refer to the prescribing information for cisplatin. elect Important afety Information Myelosuppression and Increased Risk of Myelosuppression without Vitamin upplementation ALIMTA can cause severe myelosuppression resulting in a requirement for transfusions and which may lead to neutropenic infection. The risk of myelosuppression is increased in patients who do not receive vitamin supplementation. Prior to treatment with ALIMTA, patients must be instructed to initiate supplementation with oral folic acid. Intramuscular injections of vitamin are also required prior to ALIMTA treatment. Folic acid and vitamin supplementation should be continued during treatment and for 21 days after the last dose of ALIMTA as they may reduce the severity of treatment-related hematologic and gastrointestinal toxicities. Obtain a complete blood count at the beginning of each cycle. Do not administer ALIMTA until the ANC is at least 1500 cells/mm 3 and platelet count is at least 100,000 cells/mm 3. Permanently reduce ALIMTA in patients with an ANC of less than 500 cells/mm 3 or platelet count of less than 50,000 cells/mm 3 in previous cycles. In tudies JMDB and JMCH, among patients who received vitamin supplementation, incidence of Grade 3-4 neutropenia was 15% and 23%, the incidence of Grade 3-4 anemia was 6% and 4%, and incidence of Grade 3-4 thrombocytopenia was 4% and 5%, respectively. In tudy JMCH, 18% of patients in the ALIMTA arm required red blood cell transfusions compared to 7% of patients in the cisplatin arm. In tudies JMEN, PARAMOUNT, and JMEI, where all patients received vitamin supplementation, incidence of Grade 3-4 neutropenia ranged from 3% to 5%, and incidence of Grade 3-4 anemia ranged from 3% to 5%. ee Important afety Information for ALIMTA for Consumers on page 7 and for Healthcare Providers on pages 8-9. For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information and Patient Prescribing Information.

3 Treatment with ALIMTA single agent Maintenance and 2nd-line advanced nonsquamous NCLC Vitamin Regimen One week prior to chemotherapy, then about every 9 weeks during treatment A Day 1 Day 12 Day 2 Day 13 Nurse Administered Day 3 21-Day Therapy Cycle Day 14 Day 4 Day 15 Day 5 Day 16 Day 6 Day 17 Day 7 Day 18 Day 8 Day 19 Patient Administered Day 9 Day 20 Day 10 Day 21 Day 11 Dosing modification notes In patients with creatinine clearances between 45 ml/min and 79 ml/ min, avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of ALIMTA. Monitor patients more frequently for myelosuppression, renal, and gastrointestinal toxicity, if concomitant administration of ibuprofen cannot be avoided Obtain complete blood count on days 1, 8, and 15 of each cycle. Assess creatinine clearance prior to each cycle. Do not administer ALIMTA if the creatinine clearance is less than 45 ml/min Delay initiation of the next cycle of ALIMTA until recovery of nonhematologic toxicity to grade 0-2, absolute neutrophil count (ANC) is 1500 cells/mm 3 or higher, and platelet count is 100,000 cells/mm 3 or higher Upon recovery, modify the dosage of ALIMTA in the next cycle as specified in the full Prescribing Information For dosing modifications for cisplatin, refer to the prescribing information for cisplatin Vitamin 1000 mcg injected intramuscularly (1 week prior to the first dose of ALIMTA, then once every third cycle thereafter). Do not substitute oral vitamin for intramuscular vitamin. Folic Acid mcg PO daily (beginning 7 days preceding the first dose of ALIMTA, during full course of therapy, and for 21 days after the last dose of ALIMTA) A ALIMTA 500 mg/m 2 IV over 10 minutes (every 21 days) Dexamethasone 4 mg PO BID (the day before, the day (or equivalent) of, and the day after ALIMTA) Dosing and administration for ALIMTA as a single agent: The recommended dose of ALIMTA is 500 mg/m 2 IV on day 1 of each 21-day cycle. ALIMTA is indicated for the maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy, as a single agent. ALIMTA is indicated for the treatment of patients with recurrent metastatic nonsquamous non-small cell lung cancer (NCLC) after prior chemotherapy, as a single agent. Limitation of Use: ALIMTA is not indicated for the treatment of patients with squamous cell non-small cell lung cancer. elect Important afety Information Renal Failure ALIMTA can cause severe, and sometimes fatal, renal toxicity. Determine creatinine clearance before each dose and periodically monitor renal function during treatment with ALIMTA. The incidences of renal failure in clinical studies in which patients received ALIMTA with cisplatin were: 2.1% in tudy JMDB and 2.2% in tudy JMCH. The incidence of renal failure in clinical studies in which patients received ALIMTA as a single agent ranged from 0.4% to 0.6% (tudies JMEN, PARAMOUNT, and JMEI). Withhold ALIMTA in patients with a creatinine clearance of less than 45 ml/min. IV=intravenous; NCLC=non-small cell lung cancer. * Includes adenocarcinoma, large cell carcinoma, and other histologies except those with squamous cell type. In patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 ml/min or greater. There is no recommended dose for patients whose creatinine clearance is less than 45 ml/min. Until disease progression or unacceptable toxicity. 3 ee Important afety Information for ALIMTA for Consumers on page 7 and for Healthcare Providers on pages 8-9. For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information and Patient Prescribing Information.

4 Dosing modifications: Dose reductions for ALIMTA single agent or in combination with cisplatin Recommended dosage modifications for adverse reactions a Toxicity in most recent treatment cycle Myelosuppressive toxicity Absolute neutrophil count (ANC) less than 500/mm 3 and platelets greater than or equal to 50,000/mm 3 OR Platelet count less than 50,000/mm 3 without bleeding Platelet count less than 50,000/mm 3 with bleeding Recurrent grade 3 or 4 myelosuppression after two dose reductions Nonhematologic toxicity Any grade 3 or 4 toxicities EXCEPT mucositis or neurologic toxicity OR Diarrhea requiring hospitalization Grade 3 or 4 mucositis Renal toxicity Grade 3 or 4 neurologic toxicity Recurrent grade 3 or 4 nonhematologic toxicity after two dose reductions evere and life-threatening skin toxicity Interstitial pneumonitis ALIMTA dose modification for next cycle 75% of previous dose 50% of previous dose Discontinue 75% of previous dose 50% of previous dose Withhold until creatinine clearance is 45 ml/min or greater Permanently discontinue Permanently discontinue Permanently discontinue Permanently discontinue Dosing modification notes Obtain complete blood count on days 1, 8, and 15 of each cycle. Assess creatinine clearance prior to each cycle. Do not administer ALIMTA if the creatinine clearance is less than 45 ml/min Delay initiation of the next cycle of ALIMTA until recovery of nonhematologic toxicity to grade 0-2, ANC is 1500 cells/mm 3 or higher, and platelet count is 100,000 cells/mm 3 or higher Upon recovery, modify the dosage of ALIMTA in the next cycle as specified in the table on this page For dosing modifications for cisplatin, refer to the prescribing information for cisplatin a National Cancer Institute Common Toxicity Criteria for Adverse Events version 2 (NCI CTCAE v2). elect Important afety Information Bullous and Exfoliative kin Toxicity erious and sometimes fatal, bullous, blistering and exfoliative skin toxicity, including cases suggestive of tevens-johnson yndrome/toxic epidermal necrolysis can occur with ALIMTA. Permanently discontinue ALIMTA for severe and life-threatening bullous, blistering or exfoliating skin toxicity. ee Important afety Information for ALIMTA for Consumers on page 7 and for Healthcare Providers on pages 8-9. For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information and Patient Prescribing Information. 4

5 Patient Counseling Information Advise the patient to read the FDA-approved patient labeling (Patient Information). Premedication and Concomitant Medication: Instruct patients to take folic acid as directed and to keep appointments for vitamin injections to reduce the risk of treatment-related toxicity. Instruct patients of the requirement to take corticosteroids to reduce the risks of treatment-related toxicity. Myelosuppression: Inform patients of the risk of low blood cell counts and instruct them to immediately contact their physician for signs of infection, fever, bleeding, or symptoms of anemia. Renal Failure: Inform patients of the risks of renal failure, which may be exacerbated in patients with dehydration arising from severe vomiting or diarrhea. Instruct patients to immediately contact their healthcare provider for a decrease in urine output. Bullous and Exfoliative kin Disorders: Inform patients of the risks of severe and exfoliative skin disorders. Instruct patients to immediately contact their healthcare provider for development of bullous lesions or exfoliation in the skin or mucous membranes. Interstitial Pneumonitis: Inform patients of the risks of pneumonitis. Instruct patients to immediately contact their healthcare provider for development of dyspnea or persistent cough. Radiation Recall: Inform patients who have received prior radiation of the risks of radiation recall. Instruct patients to immediately contact their healthcare provider for development of inflammation or blisters in an area that was previously irradiated. Increased Risk of Toxicity with Ibuprofen in Patients with Renal Impairment: Advise patients with mild to moderate renal impairment of the risks associated with concomitant ibuprofen use and instruct them to avoid use of all ibuprofen containing products for 2 days before, the day of, and 2 days following administration of ALIMTA. Embryo-Fetal Toxicity: Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ALIMTA and for 6 months after the final dose. Advise females to inform their prescriber of a known or suspected pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with ALIMTA and for 3 months after the final dose. Lactation: Advise women not to breastfeed during treatment with ALIMTA and for 1 week after the last dose. Preparation for Administration ALIMTA is a cytotoxic drug. Follow applicable special handling and disposal procedures. Calculate the dose of ALIMTA and determine the number of vials needed. Reconstitute ALIMTA to achieve a concentration of 25 mg/ml as follows: Reconstitute each 100-mg vial with 4.2 ml of 0.9% odium Chloride Injection, UP (preservative-free) Reconstitute each 500-mg vial with 20 ml of 0.9% odium Chloride Injection, UP (preservative-free) Do not use calcium-containing solutions for reconstitution. Gently swirl each vial until the powder is completely dissolved. The resulting solution is clear and ranges in color from colorless to yellow or green-yellow. FURTHER DILUTION I REQUIRED prior to administration. tore reconstituted, preservative-free product under refrigerated conditions [2-8 C (36-46 F)] for no longer than 24 hours from the time of reconstitution. Discard vial after 24 hours. Inspect reconstituted product visually for particulate matter and discoloration prior to further dilution. If particulate matter is observed, discard vial. Withdraw the calculated dose of ALIMTA from the vial(s) and discard vial with any unused portion. Further dilute ALIMTA with 0.9% odium Chloride Injection (preservative-free) to achieve a total volume of 100 ml for intravenous infusion. tore diluted, reconstituted product under refrigerated conditions [2-8 C (36-46 F)] for no more than 24 hours from the time of reconstitution. Discard after 24 hours. Reference: ALIMTA (pemetrexed for injection) [package insert]. Indianapolis, IN: Eli Lilly and Company; ee Important afety Information for ALIMTA for Consumers on page 7 and for Healthcare Providers on pages 8-9. For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information and Patient Prescribing Information. 5

6 ALIMTA Therapy Calendar for Janice tevenson Vitamin Regimen One week prior to chemotherapy, then about every 9 weeks during treatment Nurse Administered OV Aug DATE1 21-Day Therapy Cycle A/C Day 1 Day 12 A/C Day 2 Aug DATE8 Aug DATE9 Day 13 Vitamin Chemo Office Visit If you have questions or concerns, please call: Dr. mith: Day 3 Day 14 Day 4 Day 15 Day 5 Day 16 Day 6 Day 17 DATE Day 7 Day 18 Day 8 Day 19 Patient Administered Folic Acid Corticosteroid Day 9 Day 20 Day 10 Given by a shot into your muscle ALIMTA/cisplatin - Given by IV (1o min ALIMTA, rest, cisplatin) Come back on August 15 Aug 7 Day 21 Aug DATE28 OV Aug 15 take every day Notes to discuss with healthcare team: On your next visit, ask Nurse Johnson about the ALIMTA Therapy Guide take in the morning and evening ee Important afety Information for ALIMTA for Consumers on page 7 and for Healthcare Providers on pages 8-9. For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information and Patient Prescribing Information. Day 11 EXAMPLE CALENDAR I FOR OFFICE UE ONLY Indications ALIMTA is approved by the FDA in combination with cisplatin (another chemotherapy drug) for the first (initial) treatment of advanced nonsquamous non-small cell lung cancer (NCLC), a specific type of NCLC that has spread. ALIMTA is approved by the FDA as a single agent (used alone) for maintenance treatment of patients with advanced nonsquamous non-small cell lung cancer (NCLC) after you have received 4 cycles of chemotherapy that contains platinum for first treatment and your cancer has not progressed. ALIMTA is approved by the FDA as a single agent (used alone) for the treatment of patients with recurrent, metastatic nonsquamous non-small cell lung cancer (NCLC), a specific type of NCLC, which has returned or spread after prior chemotherapy. ALIMTA is not appropriate for people who have a different type of NCLC called squamous cell. ALIMTA is approved by the FDA for the first (initial) treatment of a kind of cancer called malignant pleural mesothelioma (MPM), which affects the lining of the lungs and chest wall. ALIMTA is used in combination with cisplatin, another anticancer medicine (chemotherapy), when surgery is not an option. elect Important afety Information Interstitial Pneumonitis erious interstitial pneumonitis, including fatal cases, can occur with ALIMTA treatment. Withhold ALIMTA for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, or fever pending diagnostic evaluation. If pneumonitis is confirmed, permanently discontinue ALIMTA. 6

7 ALIMTA Therapy Calendar for Vitamin Regimen One week prior to chemotherapy, then about every 9 weeks during treatment DATE 21-Day Therapy Cycle Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 DATE Day 7 Day 8 Day 9 Day 10 DATE DATE Day 12 Day 13 Day 14 Day 15 Day 16 Day 17 Day 18 Day 19 Day 20 Day 21 DATE Nurse Administered Patient Administered Day 11 Indications ALIMTA is approved by the FDA in combination with cisplatin (another chemotherapy drug) for the first (initial) treatment of advanced nonsquamous non-small cell lung cancer (NCLC), a specific type of NCLC that has spread. ALIMTA is approved by the FDA as a single agent (used alone) for maintenance treatment of patients with advanced nonsquamous non-small cell lung cancer (NCLC) after you have received 4 cycles of chemotherapy that contains platinum for first treatment and your cancer has not progressed. ALIMTA is approved by the FDA as a single agent (used alone) for the treatment of patients with recurrent, metastatic nonsquamous non-small cell lung cancer (NCLC), a specific type of NCLC, which has returned or spread after prior chemotherapy. ALIMTA is not appropriate for people who have a different type of NCLC called squamous cell. ALIMTA is approved by the FDA for the first (initial) treatment of a kind of cancer called malignant pleural mesothelioma (MPM), which affects the lining of the lungs and chest wall. ALIMTA is used in combination with cisplatin, another anticancer medicine (chemotherapy), when surgery is not an option. Vitamin Folic Acid elect Important afety Information Low blood cell counts OV Chemo Office Visit Corticosteroid Notes to discuss with healthcare team: Low blood cell counts can be severe, including low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and low red blood cell counts (anemia). Your healthcare provider will do blood tests to check your blood cell counts regularly during your treatment with ALIMTA. Tell your healthcare provider right away if you have any signs of infection, fever, bleeding, or severe tiredness during your treatment with ALIMTA. If you have questions or concerns, please call: ee Important afety Information for ALIMTA for Consumers on page 7 and for Healthcare Providers on pages 8-9. For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information and Patient Prescribing Information. 7

8 Important afety Information for ALIMTA (pemetrexed for injection) for patients and caregivers What is the most important information that I should know about ALIMTA? ALIMTA can cause serious side effects including: Low blood cell counts. Low blood cell counts can be severe, including low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and low red blood cell counts (anemia). Your healthcare provider will do blood tests to check your blood cell counts regularly during your treatment with ALIMTA. Tell your healthcare provider right away if you have any signs of infection, fever, bleeding, or severe tiredness during your treatment with ALIMTA. Kidney problems, including kidney failure. ALIMTA can cause severe kidney problems that can lead to death. evere vomiting or diarrhea can lead to loss of fluids (dehydration) which may cause kidney problems to become worse. Tell your healthcare provider right away if you have a decrease in amount of urine. evere skin reactions. evere skin reactions that may lead to death can happen with ALIMTA. Tell your healthcare provider right away if you develop blisters, skin sores, skin peeling, or painful sores, or ulcers in your mouth, nose, throat or genital area. Lung problems (pneumonitis). ALIMTA can cause serious lung problems that can lead to death. Tell your healthcare provider right away if you get any new or worsening symptoms of shortness of breath, cough, or fever. Radiation recall. Radiation recall is a skin reaction that can happen in people who have received radiation treatment in the past and are treated with ALIMTA. Tell your healthcare provider if you get swelling, blistering, or a rash that looks like a sunburn in an area that was previously treated with radiation. Who should not take ALIMTA? ALIMTA may not be appropriate for some patients. If you are allergic to pemetrexed, tell your doctor because you should not receive it. It is not known if ALIMTA is safe and effective in children. 8 What should I tell my health care provider doctor before receiving ALIMTA? Before receiving ALIMTA, tell your healthcare provider about all of your medical conditions including: o o o o if you have kidney problems. if you have had radiation therapy. if you think you are pregnant, or are planning to become pregnant as ALIMTA can harm your unborn baby. n Females who are able to become pregnant should use effective birth control (contraception) during treatment with ALIMTA and for 6 months after the final dose. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with ALIMTA. n Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment with ALIMTA and for 3 months after the final dose. if you are breastfeeding or plan to breastfeed, as it is not known if ALIMTA passes into breast milk. Do not breastfeed during treatment with ALIMTA and for 1 week after the final dose. Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tell your healthcare provider if you have kidney problems and take a medicine that contains ibuprofen. You should avoid taking ibuprofen for 2 days before, the day of, and 2 days after receiving treatment with ALIMTA. How is ALIMTA given? It is very important to take folic acid by mouth and receive vitamin injections from your healthcare provider during your treatment with ALIMTA to lower your risk of harmful side effects. Your healthcare provider will prescribe a medicine called a corticosteroid for you to take 2 times a day for 3 days, beginning the day before each treatment with ALIMTA. ALIMTA is given to you by intravenous (IV) infusion (injection) into your vein. The infusion is given over 10 minutes. You will usually receive ALIMTA once every 21 days (3 weeks). What are the possible side effects of ALIMTA? The most common side effects of ALIMTA when given alone are: Tiredness Nausea Loss of appetite The most common side effects of ALIMTA when given with cisplatin are: Vomiting welling or sores in your mouth or sore throat Constipation ALIMTA may cause fertility problems in males. This may affect your ability to father a child. It is not known if these effects are reversible. Talk to your healthcare provider if this is a concern for you. Your healthcare provider will do blood tests to check for side effects during treatment with ALIMTA. Your healthcare provider may change your dose of ALIMTA, delay treatment, or stop treatment if you have certain side effects. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the side effects of ALIMTA. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit medwatch, or call FDA ALIMTA is available by prescription only. For more information about all of the side effects of ALIMTA, please talk with your healthcare team, see the Patient Prescribing Information and full Prescribing Information, visit or call PM_CON_II_All_16OCT2017 Low white blood cell counts (neutropenia) Low platelet counts (thrombocytopenia) Low red blood cell counts (anemia)

9 Important afety Information for ALIMTA (pemetrexed for injection) for healthcare professionals Contraindication ALIMTA is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed. WARNING AND PRECAUTION Myelosuppression and Increased Risk of Myelosuppression without Vitamin upplementation ALIMTA can cause severe myelosuppression resulting in a requirement for transfusions and which may lead to neutropenic infection. The risk of myelosuppression is increased in patients who do not receive vitamin supplementation. Prior to treatment with ALIMTA, patients must be instructed to initiate supplementation with oral folic acid. Intramuscular injections of vitamin are also required prior to ALIMTA treatment. Folic acid and vitamin supplementation should be continued during treatment and for 21 days after the last dose of ALIMTA as they may reduce the severity of treatment-related hematologic and gastrointestinal toxicities. Obtain a complete blood count at the beginning of each cycle. Do not administer ALIMTA until the ANC is at least 1500 cells/mm 3 and platelet count is at least 100,000 cells/ mm 3. Permanently reduce ALIMTA in patients with an ANC of less than 500 cells/mm3 or platelet count of less than 50,000 cells/mm 3 in previous cycles. In tudies JMDB and JMCH, among patients who received vitamin supplementation, incidence of Grade 3-4 neutropenia was 15% and 23%, the incidence of Grade 3-4 anemia was 6% and 4%, and incidence of Grade 3-4 thrombocytopenia was 4% and 5%, respectively. In tudy JMCH, 18% of patients in the ALIMTA arm required red blood cell transfusions compared to 7% of patients in the cisplatin arm. In tudies JMEN, PARAMOUNT, and JMEI, where all patients received vitamin supplementation, incidence of Grade 3-4 neutropenia ranged from 3% to 5%, and incidence of Grade 3-4 anemia ranged from 3% to 5%. Renal Failure ALIMTA can cause severe, and sometimes fatal, renal toxicity. Determine creatinine clearance before each dose and periodically monitor renal function during treatment with ALIMTA. The incidences of renal failure in clinical studies in which patients received ALIMTA with cisplatin were: 2.1% in tudy JMDB and 2.2% in tudy JMCH. The incidence of renal failure in clinical studies in which patients received ALIMTA as a single agent ranged from 0.4% to 0.6% (tudies JMEN, PARAMOUNT, and JMEI). Withhold ALIMTA in patients with a creatinine clearance of less than 45 ml/min. Bullous and Exfoliative kin Toxicity erious and sometimes fatal, bullous, blistering and exfoliative skin toxicity, including cases suggestive of tevens-johnson yndrome/toxic epidermal necrolysis can occur with ALIMTA. Permanently discontinue ALIMTA for severe and life-threatening bullous, blistering or exfoliating skin toxicity. Interstitial Pneumonitis erious interstitial pneumonitis, including fatal cases, can occur with ALIMTA treatment. Withhold ALIMTA for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, or fever pending diagnostic evaluation. If pneumonitis is confirmed, permanently discontinue ALIMTA. Radiation Recall Radiation recall can occur with ALIMTA in patients who have received radiation weeks to years previously. Monitor patients for inflammation or blistering in areas of previous radiation treatment. Permanently discontinue ALIMTA for signs of radiation recall. Increased Risk of Toxicity with Ibuprofen in Patients with Renal Impairment Exposure to ALIMTA is increased in patients with mild to moderate renal impairment who take concomitant ibuprofen, increasing the risks of adverse reactions of ALIMTA. In patients with creatinine clearances between 45 ml/min and 79 ml/min, avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of ALIMTA. If concomitant ibuprofen use cannot be avoided, monitor patients more frequently for ALIMTA adverse reactions, including myelosuppression, renal, and gastrointestinal toxicity. Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, ALIMTA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous administration of pemetrexed to pregnant mice during the period of organogenesis was teratogenic, resulting in developmental delays and increased malformations at doses lower than the recommended human dose of 500 mg/m 2. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with ALIMTA and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ALIMTA and for 3 months after the final dose. DRUG INTERACTION Ibuprofen increases exposure (AUC) of pemetrexed. In patients with creatinine clearance between 45 ml/min and 79 ml/min: Avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of ALIMTA. Monitor patients more frequently for myelosuppression, renal, and gastrointestinal toxicity, if concomitant administration of ibuprofen cannot be avoided. ADVERE REACTION evere adverse reactions (grades 3-4) occurring in fully vitamin supplemented patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NCLC) receiving ALIMTA in combination with cisplatin versus gemcitabine in combination with cisplatin for initial treatment (JMDB), respectively, were neutropenia (15% vs 27%); fatigue (7% vs 5%); nausea (7% vs 4%); vomiting (6% vs 6%); anemia (6% vs 10%); thrombocytopenia (4% vs 13%); anorexia (2% vs 1%); creatinine elevation (1% vs 1%); diarrhea (1% vs 2%); stomatitis/pharyngitis (1% vs 0%); and constipation (1% vs 0%). Common adverse reactions (all grades) occurring in 5% fully vitamin supplemented patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NCLC) receiving ALIMTA in combination with cisplatin versus gemcitabine in combination with cisplatin for initial treatment (JMDB), respectively, were nausea (56% vs 53%); fatigue (43% vs 45%); vomiting (40% vs 36%); anemia (33% vs 46%); neutropenia (29% vs 38%); anorexia (27% vs 24%); constipation (21% vs 20%); stomatitis/pharyngitis (14% vs 12%); alopecia (12% vs 21%); diarrhea (12% vs 13%); thrombocytopenia (10% vs 27%); creatinine elevation (10% vs 7%), sensory neuropathy (9% 9 (Continues on next page)

10 Important afety Information for ALIMTA (pemetrexed for injection) for healthcare professionals, continued vs 12%); taste disturbance (8% vs 9%); rash/desquamation (7% vs 8%); and dyspepsia/heartburn (5% vs 6%). evere adverse reactions (grades 3-4) occurring in patients with non-progressive locally advanced or metastatic nonsquamous non-small cell lung cancer (NCLC) receiving ALIMTA as a single agent versus placebo as maintenance treatment (JMEN), respectively, following non-alimta containing platinum-based induction therapy were anemia (3% vs 1%); neutropenia (3% vs 0%); fatigue (5% vs 1%); nausea (1% vs 1%); anorexia (2% vs 0%); infection (2% vs 0%); mucositis/stomatitis (1% vs 0%); diarrhea (1% vs 0%); and sensory neuropathy (1% vs 0%). Common adverse reactions (all grades) occurring in 5% patients with non-progressive locally advanced or metastatic nonsquamous non-small cell lung cancer (NCLC) receiving ALIMTA as a single agent versus placebo as maintenance treatment (JMEN), respectively, following non-alimta containing platinum-based induction therapy were fatigue (25% vs 11%); nausea (19% vs 6%); anorexia (19% vs 5%); anemia (15% vs 6%); increased rash/desquamation (10% vs 3%); ALT (10% vs 4%); sensory neuropathy (9% vs 4%); vomiting (9% vs 1%); increased AT (8% vs 4%); mucositis/ stomatitis (7% vs 2%); neutropenia (6% vs 0%); diarrhea (5% vs 3%); and infection (5% vs 2%). evere adverse reactions (grades 3-4) occurring in patients with non-progressive locally advanced or metastatic nonsquamous non-small cell lung cancer (NCLC) receiving ALIMTA as a single agent versus placebo as maintenance treatment (PARAMOUNT), respectively, following ALIMTA plus cisplatin induction therapy were anemia (4.8% vs 0.6%); fatigue (4.5% vs 0.6%); neutropenia (3.9% vs 0%); nausea (0.3% vs 0%); and mucositis/stomatitis (0.3% vs 0%). Common adverse reactions (all grades) occurring in 5% patients with non-progressive locally advanced or metastatic nonsquamous non-small cell lung cancer (NCLC) receiving ALIMTA as a single agent versus placebo as maintenance treatment (PARAMOUNT), respectively, following ALIMTA plus cisplatin induction therapy were fatigue (18% vs 11%); anemia (15% vs 4.8%); nausea (12% vs 2.4%); neutropenia (9% vs 0.6%); vomiting (6% vs 1.8%); mucositis/stomatitis (5% vs 2.4%); and edema (5% vs 3.6%). evere adverse reactions (grades 3-4) occurring in fully supplemented patients with recurrent metastatic nonsquamous non-small cell lung cancer (NCLC) receiving ALIMTA as a single agent versus docetaxel as 2nd-line treatment after prior chemotherapy (JMEI), respectively, were neutropenia (5% vs 40%); fatigue (5% vs 5%); anemia (4% vs 4%); nausea (3% vs 2%); anorexia (2% vs 3%); vomiting (2% vs 1%); thrombocytopenia (2% vs 0%); increased ALT (2% vs 0%); increased AT (1% vs 0%); and stomatitis/ pharyngitis (1% vs 1%). Common adverse reactions (all grades) occurring in 5% of fully supplemented patients with recurrent metastatic nonsquamous non-small cell lung cancer (NCLC) receiving ALIMTA as a single agent versus docetaxel as 2nd-line treatment after prior chemotherapy (JMEI), respectively, were fatigue (34% vs 36%); nausea (31% vs 17%); anorexia (22% vs 24%); anemia (19% vs 22%); vomiting (16% vs 12%); stomatitis/pharyngitis (15% vs 17%); rash/desquamation (14% vs 6%); diarrhea (13% vs 24%); neutropenia (11% vs 45%); fever (8% vs 8%); thrombocytopenia (8% vs 1%); increased ALT (8% vs 1%); pruritus (7% vs 2%); increased AT (7% vs 1%); constipation (6% vs 4%); and alopecia (6% vs 38%). evere adverse reactions (grades 3-4) occurring in the fully supplemented subgroup of patients with malignant pleural mesothelioma (MPM) receiving ALIMTA in combination with cisplatin versus cisplatin alone (JMCH), respectively, were neutropenia (23% vs 3%); nausea (12% vs 6%); vomiting (11% vs 4%); fatigue (10% vs 9%); thrombocytopenia (5% vs 0%); dehydration (4% vs 1%); anemia (4% vs 0%); diarrhea (4% vs 0%); stomatitis/pharyngitis (3% vs 0%); creatinine elevation (1% vs 1%); anorexia (1% vs 1%); constipation (1% vs 1%); dyspepsia (1% vs 0%); sensory neuropathy (0% vs 1%); rash (1% vs 0%); and creatinine clearance decrease (1% vs 2%). Common adverse reactions (all grades) occurring in 5% of the fully supplemented subgroup of patients with malignant pleural mesothelioma (MPM) receiving ALIMTA in combination with cisplatin versus cisplatin alone (JMCH), respectively, were nausea (82% vs 77%); vomiting (57% vs 50%); neutropenia (56% vs 13%); fatigue (48% vs 42%); anemia (26% vs 10%); thrombocytopenia (23% vs 9%); stomatitis/pharyngitis (23% vs 6%); anorexia (20% vs 14%); diarrhea (17% vs 8%); creatinine clearance decreased (16% vs 18%); rash (16% vs 5%); constipation (12% vs 7%); creatinine elevation (11% vs 10%); alopecia (11% vs 6%); sensory neuropathy (10% vs 10%); conjunctivitis (5% vs 1%); dyspepsia (5% vs 1%); dehydration (7% vs 1%); and taste disturbance (8% vs 6%). UE IN PECIFIC PATIENT POPULATION Lactation: There is no information regarding the presence of pemetrexed or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from ALIMTA, advise women not to breastfeed during treatment with ALIMTA and for one week after last dose. Males of Reproductive Potential: ALIMTA may impair fertility in males of reproductive potential. It is not known whether these effects on fertility are reversible. Pediatric Use: The safety and effectiveness of ALIMTA in pediatric patients have not been established. Adverse reactions observed in pediatric patients studied were similar to those observed in adults. Patients with Renal Impairment: ALIMTA is primarily excreted by the kidneys. Decreased renal function results in reduced clearance and greater exposure (AUC) to ALIMTA compared with patients with normal renal function. No dose is recommended for patients with creatinine clearance less than 45 ml/min. Geriatric: The incidences of Grade 3-4 anemia, fatigue, thrombocytopenia, hypertension, and neutropenia were higher in patients 65 years of age and older as compared to younger patients: in at least one of five randomized clinical trials. For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information. PM_HCP_II_All_16OCT2017 PP-PM-U /2017 Lilly UA, LLC All rights reserved. ALIMTA is a registered trademark of Eli Lilly and Company. 10